DE2444728A1 - Verfahren zur herstellung neuer antibiotisch wirksamer verbindungen - Google Patents
Verfahren zur herstellung neuer antibiotisch wirksamer verbindungenInfo
- Publication number
- DE2444728A1 DE2444728A1 DE19742444728 DE2444728A DE2444728A1 DE 2444728 A1 DE2444728 A1 DE 2444728A1 DE 19742444728 DE19742444728 DE 19742444728 DE 2444728 A DE2444728 A DE 2444728A DE 2444728 A1 DE2444728 A1 DE 2444728A1
- Authority
- DE
- Germany
- Prior art keywords
- group
- rifamycin
- piperazinyl
- carbon atoms
- groups
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 150000001875 compounds Chemical class 0.000 title claims description 73
- 238000000034 method Methods 0.000 title claims description 41
- 125000004432 carbon atom Chemical group C* 0.000 claims description 79
- -1 ethyl-2-butenyl Chemical group 0.000 claims description 72
- BTVYFIMKUHNOBZ-ODRIEIDWSA-N Rifamycin S Chemical compound O=C1C(C(O)=C2C)=C3C(=O)C=C1NC(=O)\C(C)=C/C=C/[C@H](C)[C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@H](OC(C)=O)[C@H](C)[C@@H](OC)\C=C\O[C@@]1(C)OC2=C3C1=O BTVYFIMKUHNOBZ-ODRIEIDWSA-N 0.000 claims description 53
- HJYYPODYNSCCOU-ODRIEIDWSA-N rifamycin SV Chemical class OC1=C(C(O)=C2C)C3=C(O)C=C1NC(=O)\C(C)=C/C=C/[C@H](C)[C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@H](OC(C)=O)[C@H](C)[C@@H](OC)\C=C\O[C@@]1(C)OC2=C3C1=O HJYYPODYNSCCOU-ODRIEIDWSA-N 0.000 claims description 53
- BTVYFIMKUHNOBZ-ZDHWWVNNSA-N Rifamycin S Natural products COC1C=COC2(C)Oc3c(C)c(O)c4C(=O)C(=CC(=O)c4c3C2=O)NC(=O)C(=C/C=C/C(C)C(O)C(C)C(O)C(C)C(OC(=O)C)C1C)C BTVYFIMKUHNOBZ-ZDHWWVNNSA-N 0.000 claims description 52
- 125000000217 alkyl group Chemical group 0.000 claims description 49
- 229940109171 rifamycin sv Drugs 0.000 claims description 30
- 125000002947 alkylene group Chemical group 0.000 claims description 26
- 125000003342 alkenyl group Chemical group 0.000 claims description 24
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 23
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 21
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 20
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 20
- 238000006243 chemical reaction Methods 0.000 claims description 19
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 claims description 18
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 claims description 18
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 17
- 150000003839 salts Chemical class 0.000 claims description 17
- 125000001118 alkylidene group Chemical group 0.000 claims description 16
- 239000002253 acid Substances 0.000 claims description 14
- 150000001412 amines Chemical class 0.000 claims description 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
- HJYYPODYNSCCOU-ZDHWWVNNSA-N Rifamycin SV Natural products COC1C=COC2(C)Oc3c(C)c(O)c4c(O)c(NC(=O)C(=C/C=C/C(C)C(O)C(C)C(O)C(C)C(OC(=O)C)C1C)C)cc(O)c4c3C2=O HJYYPODYNSCCOU-ZDHWWVNNSA-N 0.000 claims description 12
- 125000004450 alkenylene group Chemical group 0.000 claims description 12
- 239000001257 hydrogen Substances 0.000 claims description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 11
- 125000002070 alkenylidene group Chemical group 0.000 claims description 11
- 229940100198 alkylating agent Drugs 0.000 claims description 10
- 239000002168 alkylating agent Substances 0.000 claims description 10
- 229910052799 carbon Inorganic materials 0.000 claims description 9
- 229960003292 rifamycin Drugs 0.000 claims description 9
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 8
- 229960005070 ascorbic acid Drugs 0.000 claims description 8
- 235000010323 ascorbic acid Nutrition 0.000 claims description 8
- 239000011668 ascorbic acid Substances 0.000 claims description 8
- 229930189077 Rifamycin Natural products 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 7
- 239000000460 chlorine Substances 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical group 0.000 claims description 5
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 5
- 239000011541 reaction mixture Substances 0.000 claims description 5
- 239000007858 starting material Substances 0.000 claims description 5
- 150000005208 1,4-dihydroxybenzenes Chemical class 0.000 claims description 4
- 125000006176 2-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Chemical group 0.000 claims description 4
- 150000002430 hydrocarbons Chemical group 0.000 claims description 4
- 239000012442 inert solvent Substances 0.000 claims description 4
- 238000002955 isolation Methods 0.000 claims description 4
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 claims description 3
- 125000001931 aliphatic group Chemical group 0.000 claims description 3
- 125000004429 atom Chemical group 0.000 claims description 3
- 125000000654 isopropylidene group Chemical group C(C)(C)=* 0.000 claims description 3
- 150000004885 piperazines Chemical class 0.000 claims description 3
- 150000003242 quaternary ammonium salts Chemical class 0.000 claims description 3
- 125000006031 2-methyl-3-butenyl group Chemical group 0.000 claims description 2
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 2
- 239000005977 Ethylene Substances 0.000 claims description 2
- 238000007126 N-alkylation reaction Methods 0.000 claims description 2
- IYABWNGZIDDRAK-UHFFFAOYSA-N allene Chemical group C=C=C IYABWNGZIDDRAK-UHFFFAOYSA-N 0.000 claims description 2
- 125000001246 bromo group Chemical group Br* 0.000 claims description 2
- 150000005690 diesters Chemical class 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 2
- 230000000269 nucleophilic effect Effects 0.000 claims description 2
- 239000003960 organic solvent Substances 0.000 claims description 2
- 230000003647 oxidation Effects 0.000 claims description 2
- 238000007254 oxidation reaction Methods 0.000 claims description 2
- 125000004334 oxygen containing inorganic group Chemical group 0.000 claims description 2
- 238000006467 substitution reaction Methods 0.000 claims description 2
- 150000003512 tertiary amines Chemical class 0.000 claims description 2
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims 2
- ROOXNKNUYICQNP-UHFFFAOYSA-N ammonium persulfate Chemical compound [NH4+].[NH4+].[O-]S(=O)(=O)OOS([O-])(=O)=O ROOXNKNUYICQNP-UHFFFAOYSA-N 0.000 claims 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims 1
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims 1
- 229910001870 ammonium persulfate Inorganic materials 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 239000011630 iodine Chemical group 0.000 claims 1
- 229910052740 iodine Inorganic materials 0.000 claims 1
- 239000000463 material Substances 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 22
- 239000000243 solution Substances 0.000 description 20
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 18
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 18
- 239000007795 chemical reaction product Substances 0.000 description 13
- 238000002211 ultraviolet spectrum Methods 0.000 description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- 239000000203 mixture Substances 0.000 description 11
- 239000002585 base Substances 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 230000003115 biocidal effect Effects 0.000 description 6
- SIHHLZPXQLFPMC-UHFFFAOYSA-N chloroform;methanol;hydrate Chemical compound O.OC.ClC(Cl)Cl SIHHLZPXQLFPMC-UHFFFAOYSA-N 0.000 description 6
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 239000008101 lactose Substances 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 239000004215 Carbon black (E152) Substances 0.000 description 4
- 239000001856 Ethyl cellulose Substances 0.000 description 4
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 4
- 235000021355 Stearic acid Nutrition 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 230000002365 anti-tubercular Effects 0.000 description 4
- 150000001721 carbon Chemical group 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 235000019325 ethyl cellulose Nutrition 0.000 description 4
- 229920001249 ethyl cellulose Polymers 0.000 description 4
- 229930195733 hydrocarbon Natural products 0.000 description 4
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 4
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 4
- 239000008117 stearic acid Substances 0.000 description 4
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 150000004053 quinones Chemical class 0.000 description 3
- XUBKCCSAVNRWOX-BVHPQESASA-N rifandin Chemical compound O([C@](C1=O)(C)O/C=C/[C@@H]([C@H]([C@@H](OC(C)=O)[C@H](C)[C@H](O)[C@H](C)[C@@H](O)[C@@H](C)\C=C\C=C(C)/C(=O)NC=2C(O)=C3C(O)=C4C)C)OC)C4=C1C3=C(O)C=2N1CCN(CC(C)C)CC1 XUBKCCSAVNRWOX-BVHPQESASA-N 0.000 description 3
- QRHQUUUKPRHWRO-UHFFFAOYSA-N 1-(2,2-dimethylpropyl)piperazine Chemical compound CC(C)(C)CN1CCNCC1 QRHQUUUKPRHWRO-UHFFFAOYSA-N 0.000 description 2
- BLMJWLVGFVHJKW-UHFFFAOYSA-N 1-(2-ethylbutyl)piperazine Chemical compound CCC(CC)CN1CCNCC1 BLMJWLVGFVHJKW-UHFFFAOYSA-N 0.000 description 2
- FFRBMBIXVSCUFS-UHFFFAOYSA-N 2,4-dinitro-1-naphthol Chemical compound C1=CC=C2C(O)=C([N+]([O-])=O)C=C([N+]([O-])=O)C2=C1 FFRBMBIXVSCUFS-UHFFFAOYSA-N 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 241000186366 Mycobacterium bovis Species 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 241000295644 Staphylococcaceae Species 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 125000003277 amino group Chemical class 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- ISAOCJYIOMOJEB-UHFFFAOYSA-N benzoin Chemical compound C=1C=CC=CC=1C(O)C(=O)C1=CC=CC=C1 ISAOCJYIOMOJEB-UHFFFAOYSA-N 0.000 description 2
- 125000002619 bicyclic group Chemical group 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 125000000687 hydroquinonyl group Chemical group C1(O)=C(C=C(O)C=C1)* 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
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- 125000005394 methallyl group Chemical group 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
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- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- 125000004193 piperazinyl group Chemical group 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
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- 235000011152 sodium sulphate Nutrition 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 150000003460 sulfonic acids Chemical class 0.000 description 2
- 235000007586 terpenes Nutrition 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 230000001549 tubercolostatic effect Effects 0.000 description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
- 229920002554 vinyl polymer Polymers 0.000 description 2
- UWYVPFMHMJIBHE-OWOJBTEDSA-N (e)-2-hydroxybut-2-enedioic acid Chemical compound OC(=O)\C=C(\O)C(O)=O UWYVPFMHMJIBHE-OWOJBTEDSA-N 0.000 description 1
- GYMXWAWEWVRWPE-UHFFFAOYSA-N 1-(2,3-dimethylbut-2-enyl)piperazine Chemical compound CC(C)=C(C)CN1CCNCC1 GYMXWAWEWVRWPE-UHFFFAOYSA-N 0.000 description 1
- BDUPBRUUHCULKZ-UHFFFAOYSA-N 1-(2-ethylbut-2-enyl)piperazine Chemical compound CCC(=CC)CN1CCNCC1 BDUPBRUUHCULKZ-UHFFFAOYSA-N 0.000 description 1
- YMJVCFBHXQQYCI-UHFFFAOYSA-N 1-(2-ethylhex-2-enyl)piperazine Chemical compound CCCC=C(CC)CN1CCNCC1 YMJVCFBHXQQYCI-UHFFFAOYSA-N 0.000 description 1
- BSXJDRJTKIPAPK-UHFFFAOYSA-N 1-(2-methyl-3-phenylpropyl)piperazine Chemical compound C=1C=CC=CC=1CC(C)CN1CCNCC1 BSXJDRJTKIPAPK-UHFFFAOYSA-N 0.000 description 1
- OQGIVRAAJBHOTH-UHFFFAOYSA-N 1-(2-methylbutyl)piperazine Chemical compound CCC(C)CN1CCNCC1 OQGIVRAAJBHOTH-UHFFFAOYSA-N 0.000 description 1
- XDDRNZDXAFSXTO-UHFFFAOYSA-N 1-(2-methylpent-2-enyl)piperazine Chemical compound CCC=C(C)CN1CCNCC1 XDDRNZDXAFSXTO-UHFFFAOYSA-N 0.000 description 1
- HUUQNWZMQSLPMX-UHFFFAOYSA-N 1-(2-methylpropyl)piperazine Chemical compound CC(C)CN1CCNCC1 HUUQNWZMQSLPMX-UHFFFAOYSA-N 0.000 description 1
- QEYIMLBNNVXWJD-UHFFFAOYSA-N 1-(3-methylbutan-2-yl)piperazine Chemical compound CC(C)C(C)N1CCNCC1 QEYIMLBNNVXWJD-UHFFFAOYSA-N 0.000 description 1
- LRPGNFROBDUREU-UHFFFAOYSA-N 1-(cyclohexylmethyl)piperazine Chemical compound C1CNCCN1CC1CCCCC1 LRPGNFROBDUREU-UHFFFAOYSA-N 0.000 description 1
- NKKXGDNOMCQEPG-UHFFFAOYSA-N 1-(cyclooctylmethyl)piperazine Chemical compound C1CNCCN1CC1CCCCCCC1 NKKXGDNOMCQEPG-UHFFFAOYSA-N 0.000 description 1
- QXQAPNSHUJORMC-UHFFFAOYSA-N 1-chloro-4-propylbenzene Chemical compound CCCC1=CC=C(Cl)C=C1 QXQAPNSHUJORMC-UHFFFAOYSA-N 0.000 description 1
- ZWAQJGHGPPDZSF-UHFFFAOYSA-N 1-prop-2-enylpiperazine Chemical compound C=CCN1CCNCC1 ZWAQJGHGPPDZSF-UHFFFAOYSA-N 0.000 description 1
- FZKCAHQKNJXICB-UHFFFAOYSA-N 2,1-benzoxazole Chemical compound C1=CC=CC2=CON=C21 FZKCAHQKNJXICB-UHFFFAOYSA-N 0.000 description 1
- 125000006069 2,3-dimethyl-2-butenyl group Chemical group 0.000 description 1
- ZNQVEEAIQZEUHB-UHFFFAOYSA-N 2-ethoxyethanol Chemical compound CCOCCO ZNQVEEAIQZEUHB-UHFFFAOYSA-N 0.000 description 1
- 125000006049 2-methyl-2-pentenyl group Chemical group 0.000 description 1
- 125000005916 2-methylpentyl group Chemical group 0.000 description 1
- 125000003542 3-methylbutan-2-yl group Chemical group [H]C([H])([H])C([H])(*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- HVBSAKJJOYLTQU-UHFFFAOYSA-N 4-aminobenzenesulfonic acid Chemical compound NC1=CC=C(S(O)(=O)=O)C=C1 HVBSAKJJOYLTQU-UHFFFAOYSA-N 0.000 description 1
- WUBBRNOQWQTFEX-UHFFFAOYSA-N 4-aminosalicylic acid Chemical compound NC1=CC=C(C(O)=O)C(O)=C1 WUBBRNOQWQTFEX-UHFFFAOYSA-N 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
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- SMPJCQGFZSDIHE-GVDHMVJUSA-N [(7S,9E,11S,12R,13S,14R,15R,16R,17S,18S,19E,21Z)-26-amino-2,15,17-trihydroxy-11-methoxy-3,7,12,14,16,18,22-heptamethyl-6,23,27,29-tetraoxo-8,30-dioxa-24-azatetracyclo[23.3.1.14,7.05,28]triaconta-1(28),2,4,9,19,21,25-heptaen-13-yl] acetate Chemical compound O=C1C(C(O)=C2C)=C3C(=O)C(N)=C1NC(=O)\C(C)=C/C=C/[C@H](C)[C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@H](OC(C)=O)[C@H](C)[C@@H](OC)\C=C\O[C@@]1(C)OC2=C3C1=O SMPJCQGFZSDIHE-GVDHMVJUSA-N 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000002723 alicyclic group Chemical group 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 150000001347 alkyl bromides Chemical class 0.000 description 1
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- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
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- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
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- FLHFTXCMKFVKRP-UHFFFAOYSA-N bromomethylcyclobutane Chemical compound BrCC1CCC1 FLHFTXCMKFVKRP-UHFFFAOYSA-N 0.000 description 1
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- 239000012876 carrier material Substances 0.000 description 1
- JQXXHWHPUNPDRT-YOPQJBRCSA-N chembl1332716 Chemical compound O([C@](C1=O)(C)O\C=C/[C@@H]([C@H]([C@@H](OC(C)=O)[C@H](C)[C@H](O)[C@H](C)[C@@H](O)[C@@H](C)/C=C\C=C(C)/C(=O)NC=2C(O)=C3C(O)=C4C)C)OC)C4=C1C3=C(O)C=2\C=N\N1CCN(C)CC1 JQXXHWHPUNPDRT-YOPQJBRCSA-N 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
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- 239000006071 cream Substances 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
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- 239000003814 drug Substances 0.000 description 1
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- 125000002573 ethenylidene group Chemical group [*]=C=C([H])[H] 0.000 description 1
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- 238000007519 figuring Methods 0.000 description 1
- UQSQSQZYBQSBJZ-UHFFFAOYSA-N fluorosulfonic acid Chemical compound OS(F)(=O)=O UQSQSQZYBQSBJZ-UHFFFAOYSA-N 0.000 description 1
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- MNWFXJYAOYHMED-UHFFFAOYSA-M heptanoate Chemical compound CCCCCCC([O-])=O MNWFXJYAOYHMED-UHFFFAOYSA-M 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
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- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 150000004694 iodide salts Chemical class 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
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- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
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- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
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- 239000011707 mineral Substances 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical class C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 150000007875 phellandrene derivatives Chemical class 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical class OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 229960001225 rifampicin Drugs 0.000 description 1
- BTVYFIMKUHNOBZ-QXMMDKDBSA-N rifamycin s Chemical class O=C1C(C(O)=C2C)=C3C(=O)C=C1NC(=O)\C(C)=C/C=C\C(C)C(O)C(C)C(O)C(C)C(OC(C)=O)C(C)C(OC)\C=C/OC1(C)OC2=C3C1=O BTVYFIMKUHNOBZ-QXMMDKDBSA-N 0.000 description 1
- 229940081192 rifamycins Drugs 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 150000003505 terpenes Chemical class 0.000 description 1
- 229930006978 terpinene Natural products 0.000 description 1
- 150000003507 terpinene derivatives Chemical class 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- GCTNBVHDRFKLLK-UHFFFAOYSA-N thujane Natural products CC1CCC2(C(C)C)C1C2 GCTNBVHDRFKLLK-UHFFFAOYSA-N 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 239000000814 tuberculostatic agent Substances 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- NLVXSWCKKBEXTG-UHFFFAOYSA-N vinylsulfonic acid Chemical compound OS(=O)(=O)C=C NLVXSWCKKBEXTG-UHFFFAOYSA-N 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 235000014101 wine Nutrition 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D269/00—Heterocyclic compounds containing rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms according to more than one of groups C07D261/00 - C07D267/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Communicable Diseases (AREA)
- Pharmacology & Pharmacy (AREA)
- Oncology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH1396473A CH594676A5 (en) | 1973-09-28 | 1973-09-28 | 3-(4-Substd.-1-piperazinyl) rifamycin S and SV derivs |
| CH1396673A CH594677A5 (en) | 1973-09-28 | 1973-09-28 | 3-(4-Substd.-1-piperazinyl) rifamycin S and SV derivs |
| CH1031474A CH622797A5 (en) | 1974-07-26 | 1974-07-26 | Process for the preparation of antibiotically active rifamycin S and SV derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE2444728A1 true DE2444728A1 (de) | 1975-04-10 |
Family
ID=27176412
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19742444728 Withdrawn DE2444728A1 (de) | 1973-09-28 | 1974-09-19 | Verfahren zur herstellung neuer antibiotisch wirksamer verbindungen |
Country Status (24)
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2609210A1 (de) * | 1975-03-05 | 1976-09-23 | Lepetit Spa | Substituierte piperazinyliminorifamycine, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel |
| US7858635B2 (en) | 2005-12-22 | 2010-12-28 | Vertex Pharmaceuticals Incorporated | Spiro compounds as modulators of muscarinic receptors |
| US7858790B2 (en) | 2006-06-29 | 2010-12-28 | Vertex Pharmaceuticals Incorporated | Modulators of muscarinic receptors |
| US7879834B2 (en) | 2004-08-19 | 2011-02-01 | Vertex Pharmaceuticals Incorporated | Spiroindoline modulators of muscarinic receptors |
-
1974
- 1974-08-08 DK DK422874A patent/DK145949C/da not_active IP Right Cessation
- 1974-08-15 FI FI2416/74A patent/FI241674A7/fi unknown
- 1974-08-16 SE SE7410465A patent/SE420494B/xx unknown
- 1974-09-04 NO NO743174A patent/NO743174L/no unknown
- 1974-09-13 GB GB40048/74A patent/GB1483621A/en not_active Expired
- 1974-09-18 FR FR7431472A patent/FR2245359B1/fr not_active Expired
- 1974-09-19 DE DE19742444728 patent/DE2444728A1/de not_active Withdrawn
- 1974-09-23 OA OA55303A patent/OA04783A/xx unknown
- 1974-09-25 IL IL45735A patent/IL45735A/xx unknown
- 1974-09-25 YU YU2611/74A patent/YU39929B/xx unknown
- 1974-09-26 SU SU742062680A patent/SU644388A3/ru active
- 1974-09-26 CA CA210,125A patent/CA1055934A/en not_active Expired
- 1974-09-26 DD DD181346A patent/DD114951A5/xx unknown
- 1974-09-26 NL NL7412729A patent/NL7412729A/xx not_active Application Discontinuation
- 1974-09-26 RO RO7491068A patent/RO71721A/ro unknown
- 1974-09-26 AR AR255770A patent/AR211845A1/es active
- 1974-09-27 BG BG030425A patent/BG25231A3/xx unknown
- 1974-09-27 AT AT778874A patent/AT331406B/de not_active IP Right Cessation
- 1974-09-27 BG BG027789A patent/BG25378A3/xx unknown
- 1974-09-27 CS CS746665A patent/CS199258B2/cs unknown
- 1974-09-27 HU HU74CI1512A patent/HU175580B/hu unknown
- 1974-09-27 IE IE2012/74A patent/IE39919B1/xx unknown
- 1974-09-28 ES ES430524A patent/ES430524A1/es not_active Expired
- 1974-09-28 EG EG433/74A patent/EG11775A/xx active
- 1974-09-28 JP JP49111016A patent/JPS6012358B2/ja not_active Expired
-
1975
- 1975-05-28 AR AR258992A patent/AR223798A1/es active
- 1975-07-31 SU SU752162195A patent/SU652895A3/ru active
-
1980
- 1980-12-10 YU YU3129/80A patent/YU40242B/xx unknown
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2609210A1 (de) * | 1975-03-05 | 1976-09-23 | Lepetit Spa | Substituierte piperazinyliminorifamycine, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel |
| US7879834B2 (en) | 2004-08-19 | 2011-02-01 | Vertex Pharmaceuticals Incorporated | Spiroindoline modulators of muscarinic receptors |
| US8258148B2 (en) | 2004-08-19 | 2012-09-04 | Vertex Pharmaceutical Incorporated | Spiroindoline modulators of muscarinic receptors |
| US8497295B2 (en) | 2004-08-19 | 2013-07-30 | Vertex Pharmaceuticals Incorporated | Spiroindoline modulators of muscarinic receptors |
| US7858635B2 (en) | 2005-12-22 | 2010-12-28 | Vertex Pharmaceuticals Incorporated | Spiro compounds as modulators of muscarinic receptors |
| US7858790B2 (en) | 2006-06-29 | 2010-12-28 | Vertex Pharmaceuticals Incorporated | Modulators of muscarinic receptors |
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| Date | Code | Title | Description |
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| 8110 | Request for examination paragraph 44 | ||
| 8130 | Withdrawal |